Muscle Relaxants & Ethanol- Dr. Masserano Flashcards
Examples of acute muscle spasm
-Lower back pain
-Neck pain
-Tension headache
-TMJ
(Treat with Antispasmodic drugs)
Examples of chronic conditions
-Cerebral palsy
-Multiple sclerosis
-Spinal cord injury
-Stroke
-Fibromyalgia
-Myofascial pain syndrom
(Treat with antispasticity drugs)
When to use antispasmodic agents
-Musculoskeletal conditions
When to use antispasticity agents
-Upper motor neuron disorders
List some antispasmodic agents
- Cyclobenzaprine
- Methocarbamol
- Carisoprodol
- Chlorzoxazone
List some anti spastic agents
- Baclofen (safe in elderly)
- Dantrolene
Which two agents have both antispastic and antispasmodic properties
- Diazepam
- Tizanidine (safe in elderly)
What are 1st, 2nd, and 3rd line treatment options for both acute and chronic lower back pain
Acute pain -1st line: Tylenol/NSAIDs -2nd line: Skeletal muscle relaxants -3rd line: Opioids Chronic pain -1st line: Tylenol/ NSAIDs -2nd line: TCAs/SNRIs -3rd line: Skeletal muscle relaxants/ opioids
Diazepam (Valium) MoA
- Potentiates GABA hyperpolarization (Cl- channel) by action on the GABAa receptor
- Site of action: CNS and Spinal cord
- Treats antispasticity and antispasmodic disorders
- Sedation: Main side effect
Baclofen (Lioresal)
- Derivative of GABAb
- Decreases calcium influx and transmitter release (decreasing glutamate)
- Increases K+ efflux (Hyperpolarizing)
- Recommended for treatment of spasticity
- Do NOT abruptly DC, gradually reduce the dose
Tizanidine (Zanaflex)
- Alpha 2 agonist
- Decreases calcium flow into presynaptic neuron
- Decreasing glutamate release
Dantrolene (Dantrium)
- Inhibits RyR1 channel in skeletal muscle
- Inhibits calcium release intracellularly
- Thus inhibiting contractions
- Treatment for spasticity
- Also can treat malignant hyperthermia
- No effect on cardiac/smooth muscle (RyR2 is found here)
Black box warning with Dantrolene (Dantrium)
- Discontinue if no benefit with in 45 days
- Potential for hepatotoxicity
What do alpha 2 agonists do
- Decrease Ca++ uptake
- Decreasing glutamate release
Cyclobenzaprine (Flexril, Amrox) MoA
- Works on upper CNS
- Alpha 2 agonist
- 5HT2 antagonist
- May prolong QT interval
- Potential for serotonin syndrome (when combined with TCAs, SSRIs, SNRIs, MAOIs)
Carisoprodol (Soma) MoA and drug schedule
- Schedule IV
- Do not combine with other CNS depressants
- Potential for drug abuse, dependence, and withdrawal
Methocarbamol (Robaxin) MoA
- CNS depressant
- Treats acute musculoskeletal pain
- Can cause sedation
Palcohol
- Freeze dried alcohol
- Federally legal
- Illegal in many states
- Exceptions: NM and CO
CNS depression increases with more or less hydrocarbons?
- Increase hydrocarbons = increased CNS depression
- Isopropanol > Ethanol> Methanol
Who will have a higher blood alcohol level; an obese patient or an healthy patient
- The obese patient
- Distributed though water
- Increased fat content = decreased water content
What is the value of “r” in men vs women
- Men = 0.68
- Women = 0.55
How many grams of ethanol is in one standard drink?
-14.4 grams
What type of kinetics does ETOH follow?
- Zero order kinetics
- One drink takes about 1.5 to 2hrs to be eliminated
What enzymes are involved in the metabolism of ETOH
- Alcohol dehydrogenase
- Aldehyde dehydrogenase
Why are asians light weights?
- Higher Km for aldehyde (lower activity)
- Making them slower metabolizers
- Build up of aldehyde levels lead to poor side effects
- Deters these people from drinking
What are some effects of ETOH on the body
- Lactate acidosis
- Hyperlipidemia
- Severe liver damage
- Hypoglycemia
What is the use of fructose in alcohol overdose
- May help to rapidly reoxidize NADH to NAD
- Increasing the metabolism of alcohols metabolites
- Can increase the metabolism by up to 20%
CNS effects of ETOH
- Sedation
- Anticonvulsant
- Analgesic
- Sleep effects
Total body effects of chronic ETOH ingestion
- Liver damage
- GI tract issues
- Muscle damage
- Heart/CV effects
- Kidney
- CNS
Positive effects of ETOH use in MODERATION
- Decreases CV risk
- Improves lipid profile
- Makes blood vessels healthier
- Decreases BP
- Decreases inflammation
Wernicke-Korsakoff syndrome
-Due to malabsorption of thiamine (B1) Wernicke's disease: -Opthalmic difficulties -Ataxia of gait -Disoriented Treatment: supplement with B1
How do you treat methanol and ethylene glycol poisoning
-Competitively block alcohol dehydrogenase
What is Denatonium Benzoate
- Additive to antifreeze
- Makes it taste bitter so your dog wont eat it
MoA of Fomepizole (Antizol)
- Injection that competitively inhibits alcohol dehydrogenase
- Used in treatment of methanol/ethylene glycol poisoning
- Used in combo with hemodialysis and general supportive care
Acute drug ints with ETOH
Increases the half life of:
- Warfarin
- Tylenol
Drug ints with chronic ETOH
- Decreases half life of Tylenol
- Increases toxic quinone when ETOH leaves system
Tylenol and ETOH better explained
- Tylenol is metabolized by CYP2E1 to a toxic quinone
- Ethanol competes with Tylenol (induces CYP2E1)
- Once ETOH is eliminated the production of toxic quinone is increased (due to upregulation of CYP2E1)
Disulfiram (Antabuse)
-Blocks the conversion of acetaldehyde to acetic acid by inhibiting aldehyde dehydrogenase
Naltrexone (Revia)
- Long acting opioid antagonist
- Helps to reduce relapse rates in alcoholics
- Diminishes the “high” of ETOH
Acamprosate (Campral)
- Blocks glutamatergic N methyl D asparte receptors
- While activating GABAb receptors
- Must be abstinent from ETOH at the initiation of treatment
Varenicline (Chantix)
- Helps to reduce alcohol consumption and alcohol cravings
- Best for pts that are also trying to quit smoking
